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Functional evidence that the self-renewal gene NANOG regulates human tumor development.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2009 May; Vol. 27 (5), pp. 993-1005. - Publication Year :
- 2009
-
Abstract
- Tumor development has long been known to resemble abnormal embryogenesis. The embryonic stem cell (ESC) self-renewal gene NANOG is purportedly expressed by some epithelial cancer cells but a causal role in tumor development has remained unclear. Here, we provide compelling evidence that cultured cancer cells, as well as xenograft- and human primary prostate cancer cells express a functional variant of NANOG. NANOG mRNA in cancer cells is derived predominantly from a retrogene locus termed NANOGP8. NANOG protein is detectable in the nucleus of cancer cells and is expressed higher in patient prostate tumors than matched benign tissues. NANOGP8 mRNA and/or NANOG protein levels are enriched in putative cancer stem/progenitor cell populations. Importantly, extensive loss-of-function analysis reveals that RNA interference-mediated NANOG knockdown inhibits tumor development, establishing a functional significance for NANOG expression in cancer cells. Nanog short hairpin RNA transduced cancer cells exhibit decreased long-term clonal and clonogenic growth, reduced proliferation and, in some cases, altered differentiation. Thus, our results demonstrate that NANOG, a cell-fate regulatory molecule known to be important for ESC self-renewal, also plays a novel role in tumor development.
- Subjects :
- Animals
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Clone Cells
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Homeodomain Proteins metabolism
Humans
Hyaluronan Receptors metabolism
Male
Nanog Homeobox Protein
Pseudogenes
RNA Interference
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Small Interfering metabolism
Rats
Transcription, Genetic
Transduction, Genetic
Homeodomain Proteins genetics
Neoplasms genetics
Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4918
- Volume :
- 27
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 19415763
- Full Text :
- https://doi.org/10.1002/stem.29